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Piceatannol protects against cisplatin nephrotoxicity via activation of Nrf2/HO-1 pathway and hindering NF-κB inflammatory cascade.
Naunyn Schmiedebergs Arch Pharmacol. 2019 11; 392(11):1331-1345.NS

Abstract

This study investigates the molecular mechanisms of the nephroprotective effect of piceatannol (PIC) against cisplatin-induced nephrotoxicity in rats. PIC (10 mg/kg i.p.) was given for 7 days, starting 2 days before cisplatin single injection (7 mg/kg i.p.). Serum creatinine, blood urea nitrogen (BUN), kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin were used as nephrotoxicity markers. Oxidative stress, inflammatory, and apoptotic markers were determined. In addition, the role of PIC in Nrf2 activation and its subsequent induction of antioxidant enzymes, as well as its potential cross talk with nuclear factor kappa-B, were addressed. PIC reversed cisplatin-induced elevation of nephrotoxicity markers and restored the normal kidney ultrastructure. PIC attenuated cisplatin-induced reduction in Nrf2 expression and the relative mRNA level of antioxidant enzymes: hemeoxygenase-1, cysteine ligase catalytic, and modifier subunits, as well as superoxide dismutase and glutathione-S-transferase activities. Cisplatin pro-inflammatory response was reduced by PIC treatment as evidenced by the suppression of nuclear factor kappa-B activation and the subsequent decreased tissue levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase. PIC suppressed cisplatin-induced apoptosis by decreasing p53 and cytochrome C expression and caspase-3 activity. Therefore, PIC may protect against cisplatin-induced nephrotoxicity by modulating Nrf2/HO-1 signaling and hindering the inflammatory and apoptotic pathways.

Authors+Show Affiliations

Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt.Pharmacology & Toxicology Department, Faculty of Pharmacy, Ain Shams University, Cairo, Egypt. ebtehal_dm@yahoo.com.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31197431

Citation

Wahdan, Sara A., et al. "Piceatannol Protects Against Cisplatin Nephrotoxicity Via Activation of Nrf2/HO-1 Pathway and Hindering NF-κB Inflammatory Cascade." Naunyn-Schmiedeberg's Archives of Pharmacology, vol. 392, no. 11, 2019, pp. 1331-1345.
Wahdan SA, Azab SS, Elsherbiny DA, et al. Piceatannol protects against cisplatin nephrotoxicity via activation of Nrf2/HO-1 pathway and hindering NF-κB inflammatory cascade. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(11):1331-1345.
Wahdan, S. A., Azab, S. S., Elsherbiny, D. A., & El-Demerdash, E. (2019). Piceatannol protects against cisplatin nephrotoxicity via activation of Nrf2/HO-1 pathway and hindering NF-κB inflammatory cascade. Naunyn-Schmiedeberg's Archives of Pharmacology, 392(11), 1331-1345. https://doi.org/10.1007/s00210-019-01673-8
Wahdan SA, et al. Piceatannol Protects Against Cisplatin Nephrotoxicity Via Activation of Nrf2/HO-1 Pathway and Hindering NF-κB Inflammatory Cascade. Naunyn Schmiedebergs Arch Pharmacol. 2019;392(11):1331-1345. PubMed PMID: 31197431.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Piceatannol protects against cisplatin nephrotoxicity via activation of Nrf2/HO-1 pathway and hindering NF-κB inflammatory cascade. AU - Wahdan,Sara A, AU - Azab,Samar S, AU - Elsherbiny,Doaa A, AU - El-Demerdash,Ebtehal, Y1 - 2019/06/14/ PY - 2019/03/27/received PY - 2019/06/04/accepted PY - 2019/6/15/pubmed PY - 2020/8/21/medline PY - 2019/6/15/entrez KW - Cisplatin KW - Inflammation KW - Nephrotoxicity KW - Oxidative stress KW - Piceatannol SP - 1331 EP - 1345 JF - Naunyn-Schmiedeberg's archives of pharmacology JO - Naunyn Schmiedebergs Arch Pharmacol VL - 392 IS - 11 N2 - This study investigates the molecular mechanisms of the nephroprotective effect of piceatannol (PIC) against cisplatin-induced nephrotoxicity in rats. PIC (10 mg/kg i.p.) was given for 7 days, starting 2 days before cisplatin single injection (7 mg/kg i.p.). Serum creatinine, blood urea nitrogen (BUN), kidney injury molecule 1, and neutrophil gelatinase-associated lipocalin were used as nephrotoxicity markers. Oxidative stress, inflammatory, and apoptotic markers were determined. In addition, the role of PIC in Nrf2 activation and its subsequent induction of antioxidant enzymes, as well as its potential cross talk with nuclear factor kappa-B, were addressed. PIC reversed cisplatin-induced elevation of nephrotoxicity markers and restored the normal kidney ultrastructure. PIC attenuated cisplatin-induced reduction in Nrf2 expression and the relative mRNA level of antioxidant enzymes: hemeoxygenase-1, cysteine ligase catalytic, and modifier subunits, as well as superoxide dismutase and glutathione-S-transferase activities. Cisplatin pro-inflammatory response was reduced by PIC treatment as evidenced by the suppression of nuclear factor kappa-B activation and the subsequent decreased tissue levels of interleukin-1β, tumor necrosis factor-α, cyclooxygenase-2, and inducible nitric oxide synthase. PIC suppressed cisplatin-induced apoptosis by decreasing p53 and cytochrome C expression and caspase-3 activity. Therefore, PIC may protect against cisplatin-induced nephrotoxicity by modulating Nrf2/HO-1 signaling and hindering the inflammatory and apoptotic pathways. SN - 1432-1912 UR - https://www.unboundmedicine.com/medline/citation/31197431/Piceatannol_protects_against_cisplatin_nephrotoxicity_via_activation_of_Nrf2/HO_1_pathway_and_hindering_NF_κB_inflammatory_cascade_ L2 - https://dx.doi.org/10.1007/s00210-019-01673-8 DB - PRIME DP - Unbound Medicine ER -